Triterpene glycosides from the Vietnamese sea cucumber Holothuria edulis

Abstract

From the MeOH extract of the Vietnamese sea cucumber Holothuria edulis, eight triterpene glycosides (1–8), including one new compound namely holothurin A₅ (1), were isolated by using various chromatographic separations. Their structures were established by spectroscopic experiments including 1D, 2D NMR and HR-ESI-MS. Holothurin A₅ (1) has a hydroperoxy group at C-25. To the best of our knowledge, this is the first report of this group in triterpene saponins obtained from sea cucumbers to date. In addition, the in vitro cytotoxicity against five human cancer cell lines (HepG2, KB, LNCaP, MCF7 and SK-Mel2) of all isolated compounds was also evaluated using SRB assays.     

Pullback Attractors for Stochastic Young Differential Delay Equations

We study the asymptotic dynamics of stochastic Young differential delay equations under the regular assumptions on Lipschitz continuity of the coefficient functions. Our main results show that, if there is a linear part in the drift term which has no delay factor and has eigenvalues of negative real parts, then the generated random dynamical system possesses a random pullback attractor provided that the Lipschitz coefficients of the remaining parts are small.

     

Heat and mass transfer problems in solution growth of GaP crystals by the travelling solvent method (TSM)

The influence of the natural convection on the heat and mass transfer process during growth of GaP crystals from the solution is considered. The two-dimensional quasi-stationary thermodiffusive hydrodynamic problem for the GaP growth system by travelling solvent method (TSM), as a model, has been solved. Computation is given for the temperature and concentration field distribution in the solution. The picture of vortex configuration for different lengths of the liquid zone, the shape of the growing and dissolving interfaces and also the boundary layers thickness are obtained. The experimental dependence of the growth rate on the convection intensity observed mostly confirmed the calculation results.     

Target Design of Novel Histone Deacetylase 6 Selective Inhibitors with 2-Mercaptoquinazolinone as the Cap Moiety

Epigenetic alterations found in all human cancers are promising targets for anticancer therapy. In this sense, histone deacetylase inhibitors (HDACIs) are interesting anticancer agents that play an important role in the epigenetic regulation of cancer cells. Here, we report 15 novel hydroxamic acid-based histone deacetylase inhibitors with quinazolinone core structures. Five compounds exhibited antiproliferative activity with IC₅₀ values of 3.4–37.8 µM. Compound 8 with a 2-mercaptoquinazolinone cap moiety displayed the highest antiproliferative efficacy against MCF-7 cells. For the HDAC6 target selectivity study, compound 8 displayed an IC₅₀ value of 2.3 µM, which is 29.3 times higher than those of HDAC3, HDAC4, HDAC8, and HDAC11. Western blot assay proved that compound 8 strongly inhibited tubulin acetylation, a substrate of HDAC6. Compound 8 also displayed stronger inhibition activity against HDAC11 than the control drug Belinostat. The inhibitory mechanism of action of compound 8 on HDAC enzymes was then explored using molecular docking study. The data revealed a high binding affinity (−7.92 kcal/mol) of compound 8 toward HDAC6. In addition, dock pose analysis also proved that compound 8 might serve as a potent inhibitor of HDAC11.     

Photoinitiated cationic polymerisation of multifunctional systems

Different types of tridimensional polymer networks have been synthetised by photoinitiated cationic polymerisation of vinyl ether and epoxy-functionalised oligomers and polymers. The polymerisation kinetics was followed by real-time infrared (RTIR) spectroscopy, a technique that records directly conversion versus time profiles in a timescale as short as 1 s. The addition of a diacrylate monomer was shown to accelerate the ring-opening polymerisation of epoxidized polyisoprene, with formation of interpenetrating polymer networks having well contrasted properties. A dual polymer network has been generated by photocrosslinking of a polyisoprene functionalised with both epoxy and acrylate groups.     

Differential effects of various trivalent and pentavalent organic and inorganic arsenic species on glucose metabolism in isolated kidney cells

We have compared the acute toxicities of the trivalent arsenic species arsenite, oxophenylarsine (PhAsO), 2-chlorovinyloxoarsine (ClvinAsO), methyloxoarsine (MeAsO), and of the pentavalent arsenic species arsenate, methyl- and phenyl-arsonic acid in rat kidney tubules (RKT) and Madin-Darby canine kidney (MDCK) cells. In RKT, PhAsO (1 μmol I⁻¹, 60 min) almost completely (>90%) blocked gluconeogenesis without affecting cell viability as assessed by dye exclusion. In MDCK cells, PhAsO (2 μmol I⁻¹) markedly inhibited glucose uptake (60% of controls) within 30 min, while cell viability, as assessed by formazan formation, was not affected within 180 min. MeAsO and CIvinAsO were similarly effective to PhAsO in both RKT and MDCK cells. Estimated IC₅₀ values for the inhibition of gluconeogenesis were 0.55 (PhAsO), 0.69 (CIvinAsO) and 0.99 μmol I⁻¹ (MeAsO) and for the inhibition of glucose uptake 1.23 (PhAsO). 2.62 (CIvinAsO) and 6.99 μmol I⁻¹ (MeAsO). At longer storage times, aqueous solutions of MeAsO and of CIvinAsO, but not of PhAsO, gradually lost toxic activity in RKT and MDCK cells, especially at alkaline pH. Concomitantly, a gradual decrease in content as assessed by HPLC was detected. Roughly 10-fold higher concentrations of arsenite than of PhAsO were required for comparable effects on gluconeogenesis in RKT, whereas in MDCK cells about 100-fold higher concentrations were needed for similar inhibition of glucose uptake. Pentavalent arsenate and phenylarsonate were two orders of magnitude less effective than PhAsO in RKT, while methylarsonate had virtually no influence on gluconeogenic activity. In MDCK cells the pentavalent arsenic species showed effects only in the millimolar range. It is concluded (1) that different mechanisms are involved in the acute toxicity of oxoarsines and inorganic arsenic and (2) that PhAsO offers advantages as a model substance for mono-substituted trivalent arsenicals, because it is more stable and more readily detectable.     

Ring-opening metathesis copolymerization employing ruthenium-based metathesis catalysts

The copolymerization of both high- and low-strain cyclic olefins employing three ruthenium-based metathesis catalysts is desribed. The effect of the ligand environment as well as the nature of the carbene on the copolymerizations is discussed.